Details of the Drug

General Information of Drug (ID: DM2EXC5)

Drug Name

BOL-303259-X

Synonyms

Latanoprostene bunod; Latanoprostene bunod); NCX-116; PF-03187207; PF-3187207; BOL-303259-X1; NO donors (glaucoma), NicOx/Pfizer; NO-donating prostaglandin F2-alpha analogs (glaucoma), Pfizer; NO-donating prostaglandin F2-alpha analogs (glaucoma), NicOx/Pfizer; Nitric oxide-donating prostaglandin F2-alpha analogs (eye disease), NicOx/Pfizer; NO-donating prostaglandin F2-alpha analogs (glaucoma), NicOx/ Bausch & Lomb

Indication

Disease Entry	ICD 11	Status	REF
Open-angle glaucoma	9C61	Approved	[1]
Renal cell carcinoma	2C90	Phase 3	[2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

507.6

Topological Polar Surface Area (xlogp)

4.4

Rotatable Bond Count (rotbonds)

18

Hydrogen Bond Donor Count (hbonddonor)

3

Hydrogen Bond Acceptor Count (hbondacc)

8

ADMET Property

Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 59.1 ng/L [3]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 5 min [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 1.8 hours (in rabbits cornea), 2.1 hours (in rabbits aqueous humor), and 4.6 hours (in rabbits iris/ciliary body) [4]
Metabolism: The drug is metabolized via the endogenous corneal esterases into latanoprost acid and butanediol mononitrate [3]

Chemical Identifiers

Formula: C27H41NO8
IUPAC Name: 4-nitrooxybutyl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]hept-5-enoate
Canonical SMILES: C1[C@H]([C@@H]([C@H]([C@H]1O)C/C=C\\CCCC(=O)OCCCCO[N+](=O)[O-])CC[C@H](CCC2=CC=CC=C2)O)O
InChI: InChI=1S/C27H41NO8/c29-22(15-14-21-10-4-3-5-11-21)16-17-24-23(25(30)20-26(24)31)12-6-1-2-7-13-27(32)35-18-8-9-19-36-28(33)34/h1,3-6,10-11,22-26,29-31H,2,7-9,12-20H2/b6-1-/t22-,23+,24+,25-,26+/m0/s1
InChIKey: LOVMMUBRQUFEAH-UIEAZXIASA-N

Cross-matching ID

PubChem CID: 11156438
CAS Number: 860005-21-6
DrugBank ID: DB11660
TTD ID: D05LQX
VARIDT ID: DR00093
ACDINA ID: D01200

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prostaglandin F2-alpha receptor (PTGFR)	TTT2ZAR	PF2R_HUMAN	Agonist	[5]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[6]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Open-angle glaucoma

ICD Disease Classification

9C61

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Prostaglandin F2-alpha receptor (PTGFR)	DTT	PTGFR	8.25E-02	-0.05	-0.14
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTP	OATP2B1	6.30E-05	2.52E-01	5.88E-01

Molecular Expression Atlas (MEA)

MEA Detail

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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Edetic acid	E00094	6049	Antimicrobial preservative; Complexing agent
Glycerin	E00026	753	Antimicrobial preservative; Emollient; Flavoring agent; Humectant; Lubricant; Plasticizing agent; Solvent; Suppository base; Tonicity agent; Viscosity-controlling agent
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Water	E00035	962	Solvent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Latanoprostene Bunod 0.24 mg/ml solution	0.24 mg/ml	Solution	Topical

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Evaluation of the Effect of Latanoprostene Bunod Ophthalmic Solution, 0.024% in Lowering Intraocular Pressure over 24 in Healthy Japanese Subjects.Adv Ther. 2015 Nov;32(11):1128-39.
2	ClinicalTrials.gov (NCT01895972) A Study Evaluating the Long-Term Safety of Latanoprostene Bunod Ophthalmic Solution 0.024%, in Japanese Subjects With Open-Angle Glaucoma or Ocular Hypertension. U.S.National Institutes of Health.
3	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4	Critical evaluation of latanoprostene bunod in the treatment of glaucoma. Clin Ophthalmol. 2016 Oct 18;10:2035-2050. eCollection 2016.
5	Ocular hypotensive activity of BOL-303259-X, a nitric oxide donating prostaglandin F2alpha agonist, in preclinical models. Exp Eye Res. 2011 Sep;93(3):250-5.
6	The prostaglandin transporter OATP2A1 is expressed in human ocular tissues and transports the antiglaucoma prostanoid latanoprost. Invest Ophthalmol Vis Sci. 2010 May;51(5):2504-11.
7	Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60.
8	The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res. 2016 Jan 4;44(D1):D372-9. (ID: 2.A.60.1.20)
9	Small-Dosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1 and ABCG2), and Interaction (Atorvastatin and Grapefruit Juice) Profiles of 5 Probes for OATP2B1 and BCRP. J Pharm Sci. 2017 Sep;106(9):2688-2694.
10	Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
11	Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther. 2004 Feb;308(2):438-45.
12	Human platelets express organic anion-transporting peptide 2B1, an uptake transporter for atorvastatin. Drug Metab Dispos. 2009 May;37(5):1129-37.
13	pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1. Mol Pharm. 2011 Aug 1;8(4):1303-13.
14	Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006 Jul;34(7):1229-36.
15	Drug Interactions in Infectious Diseases.
16	Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab Dispos. 2008 Oct;36(10):2014-23.
17	Evaluation of WO 2012/177618 A1 and US-2014/0179750 A1: novel small molecule antagonists of prostaglandin-E2 receptor EP2.Expert Opin Ther Pat. 2015 Jul;25(7):837-44.
18	PGF(2alpha) FP receptor contributes to brain damage following transient focal brain ischemia. Neurotox Res. 2009 Jan;15(1):62-70.
19	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
20	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
21	Prostaglandin subtype-selective and non-selective IOP-lowering comparison in monkeys. J Ocul Pharmacol Ther. 2009 Feb;25(1):1-8.
22	Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydroc... J Med Chem. 2007 Feb 22;50(4):794-806.
23	Role of nitric oxide in PGF2 alpha-induced ocular hyperemia. Exp Eye Res. 1994 Oct;59(4):401-7.
24	IOP-Lowering Effect of ONO-9054, A Novel Dual Agonist of Prostanoid EP3 and FP Receptors, in Monkeys. Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2547-52.
25	THG113: a novel selective FP antagonist that delays preterm labor. Semin Perinatol. 2002 Dec;26(6):389-97.
26	Identification by site-directed mutagenesis of amino acids contributing to ligand-binding specificity or signal transduction properties of the human FP prostanoid receptor. Biochem J. 2003 Apr 15;371(Pt 2):443-9.